The principal aim of this project is to elucidate in an inbred rat model of transplantation the mechanisms by which specific unresponsiveness to alloantigens can be induced. Lymphocytes having the phenotype of the suppressor/cytotoxic subset, as marked by the monoclonal antibody OX8, effect antigen-specific feedback suppression of the mixed lymphocyte response (MLR) in vitro, and can transfer states of unresponsiveness from animals bearing functioning allografts to syngeneic recipients. We aim to dissect out and define the components of those suppressor pathways which are operative in rat models of specific unresponsiveness (induced by enhancement or cyclosporin A), and to propagate and clone the principal T cells involved for further study and possible use in vivo. We will utilize inbred, congenic and recombinant rat strains, monoclonal antibodies to T cell differentiation antigens and to MHC epitopes, affinity and flow cytometric fractionation of cells based upon surface markers, and will develop T-T hybridomas, as well as B-myeloma hybridomas for production of factors and antibody probes for as yet undefined components of the T suppressor pathways. We plan to model new approaches to defining requirements for induction and maintenance of specific unresponsiveness. Understanding of how antigen-specific suppressor systems are activated in response to alloantigens will complement similar information being gathered in other immune response and disease models, and will contribute to new approaches to clinical problems in transplantation and autoimmunity.